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Objectives: We investigated tau and neurodegeneration patterns and clinical phenotypes in carriers of a specific pathogenic variant in the PSEN1 gene and 1 nonaffected relative., Methods: We included 3 symptomatic carriers of the c.436 A>C, p.Met146Leu, NM_000021.4, rs63750306 variant in the PSEN1 gene, pathogenic for autosomal dominant Alzheimer disease (AD), 1 asymptomatic carrier of the same variant, and 1 noncarrier, all belonging to the same "N" family. All subjects underwent clinical evaluations, 18 F-flortaucipir-PET, and MRI. 18 F-fludeoxyglucose-PET was available for 3 cases., Results: All symptomatic carriers showed advanced AD tau patterns. Symptomatic female carriers presented an earlier age at onset and more pronounced tau pathology in temporoparietal and frontal regions than male carriers, at comparable disease severity and duration. The presymptomatic male carrier showed a negative tau scan 4 years before symptom onset. MRI showed no severe cortical and hippocampal atrophy in all individuals. Brain metabolism showed neurodegeneration patterns typical of AD in symptomatic carriers., Discussion: In PSEN1 Met146Leu variant carriers, high cortical tau load, without significant atrophy, was present during early memory deficits. In the asymptomatic phase, all biomarkers were negative. More pronounced tau pathology in female than male individuals highlights the need to investigate sex differences in autosomal dominant AD.

Background: Innovative digital solutions are shaping a new concept of dementia care, opening additional venues for prevention, diagnosis, monitoring and treatment. Hereby, we report the development of a tablet-based teleneuropsychology platform (Tenèpsia®), from concept to certification as Medical Device (MD) Class IIA, as per new MD regulation 745/2017., Methods: The platform was designed for the remote cognitive evaluation and created thanks to the effort of a collaborative working group including experts from three Italian scientific societies and Biogen Italia S.r.l. (hereafter "Biogen"), and developers from Xenia Reply and Inside AI. The development strategy was guided by converting traditional paper-and-pencil tests into digital versions while maintaining comparable neuropsychological features and optimizing patient accessibility and user experience. The experts focused on the choice and adaptation of traditional neuropsychology measures for a 45-min teleneuropsychology assessment., Results: The developers created a web and a mobile interface, respectively, for the professional (neuropsychologist) and non-professional (patient and caregiver) use. Recording of voice, drawing and typing information was enabled. Instant dashboards provide a quick overview of the patient's condition. Simulation activities were performed to obtain MD certification, valid across Europe., Conclusion: Neuropsychology services will benefit from the implementation in clinics of harmonized digital tools with adequate scientific and technological standards. The use of digital cognitive testing for the diagnosis of mild cognitive impairment is expected to enhance patient and clinician outcomes through simplified, digital objective data collection, sparing of time and resources, with a positive impact on healthcare costs and access to treatments, reducing inequalities and delays in diagnosis and cure., (© 2024. Fondazione Società Italiana di Neurologia.)

Alzheimer's Disease (AD) and Frontotemporal Dementia (FTD) are the two major neurodegenerative diseases with distinct clinical and neuropathological profiles. The aim of this report is to conduct a population-based investigation in well-characterized APP , PSEN1 , PSEN2 , MAPT , GRN , and C9orf72 mutation carriers/pedigrees from the north, the center, and the south of Italy. We retrospectively analyzed the data of 467 Italian individuals. We identified 21 different GRN mutations, 20 PSEN1 , 11 MAPT , 9 PSEN2 , and 4 APP . Moreover, we observed geographical variability in mutation frequencies by looking at each cohort of participants, and we observed a significant difference in age at onset among the genetic groups. Our study provides evidence that age at onset is influenced by the genetic group. Further work in identifying both genetic and environmental factors that modify the phenotypes in all groups is needed. Our study reveals Italian regional differences among the most relevant AD/FTD causative genes and emphasizes how the collaborative studies in rare diseases can provide new insights to expand knowledge on genetic/epigenetic modulators of age at onset.

Physical distancing due to the COVID-19 Pandemic has limited the opportunities for family members, friends, and significant others to show physical affection (i.e., hugs, kisses, caresses, holding hands) during social interactions. The present study investigated the effects of positive touch and psychological distress in 991 Italian participants ( M age = 34.43, SD = 14.27). Results showed the frequency of hugs with the cohabiting partner significantly decreased the symptoms of depression ( β = -1.187, p = 0.018, e β = 0.30, 95% CI = 0.11-0.82), whereas the frequency of caresses with cohabiting relatives predicted the symptoms of anxiety ( β = 0.575, p = 0.034, e β = 1.78, 95% CI = 1.04-3.03). The frequency of hugs ( β = -0.609, p = 0.049, e β = 0.54, 95% CI = 0.30-1.00), and kisses ( β = 0.663, p = 0.045, e β = 1.94, 95% CI = 1.01-3.71) with non-cohabiting relatives predicted the symptoms of anxiety ( χ 2 = 1.35, df = 5, p = 0.93). These results suggest the importance of positive touch on psychological well-being in the social context.

Although originally multi-ethnic in its structure, nowadays the Calabria region of southern Italy represents an area with low genetic heterogeneity and a high level of consanguinity that allows rare mutations to be maintained due to the founder effect. A complex research methodology-ranging from clinical activity to the genealogical reconstruction of families/populations across the centuries, the creation of databases, and molecular/genetic research-was modelled on the characteristics of the Calabrian population for more than three decades. This methodology allowed the identification of several novel genetic mutations or variants associated with neurodegenerative diseases. In addition, a higher prevalence of several hereditary neurodegenerative diseases has been reported in this population, such as Alzheimer's disease, frontotemporal dementia, Parkinson's disease, Niemann-Pick type C disease, spinocerebellar ataxia, Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker disease. Here, we summarize and discuss the results of research data supporting the view that Calabria could be considered as a genetic isolate and could represent a model, a sort of outdoor laboratory-similar to very few places in the world-useful for the advancement of knowledge on neurodegenerative diseases.

People with dementia have an increased risk of contracting severe forms of COVID-19. Although in worldwide vaccination programs priority has been given to older people, having taken the vaccine does not totally eliminate the risk of contracting COVID-19 when one is in close contact with unvaccinated people. Thus, family caregivers' choices to remain unvaccinated against COVID-19 could have potentially lethal consequences for their relatives. To our knowledge, this study represents the first attempt within the international literature to analyze COVID-19 vaccine uptake among family caregivers of people with dementia and to identify some of the psychological factors, related to COVID-19 and vaccination behavior, that could facilitate or hinder vaccine uptake. Contact information for family caregivers was obtained from five different centers and associations throughout the Italian territory. Data were collected from 179 respondents during July-September 2021 using a cross-sectional web-based survey design. More than 75% of the respondents indicated that had been vaccinated against COVID-19 and reported receiving vaccine information mainly from print or electronic newspapers (86%), followed by TV (81%) and families (64.2%). In multivariable logistic regression analyses, worries about unforeseen future effects was significantly related to COVID-19 vaccine uptake, indicating that family caregivers concerned about potential side effects of vaccines were less likely to have been vaccinated against COVID-19 (OR = 0.60, CI = 0.40-0.89). Openness to experience was also related to COVID-19 vaccine uptake, with family caregivers higher on this trait being less likely to have been vaccinated against COVID-19 (OR = 0.83, CI = 0.71-0.98). Implications for targeting of vaccine-related messages are discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bruno, Malvaso, Chiesi, Laganà, Servidio, Isella, Ferrarese, Gottardi, Stella, Agosta, Filippi, Lorenzo, Martin, Bruni and Maletta.)

Neuropsychiatric or behavioral and psychological symptoms of dementia (BPSD) represent a heterogeneous group of non-cognitive symptoms that are virtually present in all patients during the course of their disease. The aim of this study is to examine the prevalence and natural history of BPSD in a large cohort of patients with behavioral variant of frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) in three stages: (i) pre-T0 (before the onset of the disease); (ii) T0 or manifested disease (from the onset to 5 years); (iii) T1 or advanced (from 5 years onwards). Six hundred seventy-four clinical records of patients with bvFTD and 1925 with AD, from 2006 to 2018, were studied. Symptoms have been extracted from Neuropsychiatric Inventory (NPI) and from a checklist of BPSD for all periods observed. In our population, BPSD affect up to 90% of all dementia subjects over the course of their illness. BPSD profiles of the two dementia groups were similar but not identical. The most represented symptoms were apathy, irritability/affective lability, and agitation/aggression. Considering the order of appearance of neuropsychiatric symptoms in AD and bvFTD, mood disorders (depression, anxiety) come first than the other BPSD, with the same prevalence. This means that they could be an important "red flag" in detection of dementia. With the increase of disease severity, aberrant motor behavior and wandering were significantly more present in both groups. Differences between BPSD in AD and bvFTD resulted only in prevalence: Systematically, in bvFTD, all the symptoms were more represented than in AD, except for hallucinations, depression, anxiety, and irritability. Given their high frequency and impact on management and overall health care resources, BPSD should not be underestimated and considered as an additional important diagnostic and therapeutic target both in patients with AD and bvFTD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Laganà, Bruno, Altomari, Bruni, Smirne, Curcio, Mirabelli, Colao, Puccio, Frangipane, Cupidi, Torchia, Muraca, Malvaso, Addesi, Montesanto, Di Lorenzo, Bruni and Maletta.)

Despite the massive volume of scientific evidence on the benefits of immunisation, vaccine hesitancy is still a global health threat and represents an obstacle to controlling the spread of viruses such as SARS-CoV-2 and its associated COVID-19. Thus, the present study aimed to adapt and validate an Italian version of the Vaccination Attitudes Examination (VAX) scale. The Italian version of the scale (VAX-I), along with validation measures (general health perceptions, perceived sensitivity to medicines, intention to get the flu vaccine, and trust in health authorities) were administered to a sample of 534 Italian participants aged 18 to 87 ( M  = 32.41, SD  = 15.35). The original version of the VAX scale was translated into Italian using a back-translation method. The parallel and confirmatory factor analyses showed that the scale's four-factor structure fits the data well, as in the original version. Reliability coefficients indicated that the VAX-I scale showed good internal consistency and measurement invariance results demonstrated that the VAX-I scale is stable across gender. Construct validity was supported by the significant negative correlation with general health perceptions, intentions to get the flu vaccine, and trust in health authorities, and the weak but significant and positive correlation with perceived sensitivity to medicines. Overall, the VAX-I scale appears to be a valid instrument to assess vaccine hesitancy in the Italian context., Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03209-5., Competing Interests: Conflicts of InterestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. This research received no funding. We thank all those who participated in this study., (© The Author(s) 2022.)

Bergamot belongs to the Rutaceae family and is a typical fruit grown principally in the province of Reggio Calabria (South Italy). Nowadays, its industrial use is mostly related to the extraction of the essential oil contained in the flavedo but also to a lesser extent the extraction of the juice (from the pulp), which is rich in antioxidants. However, the pressed pulp (known as Pastazzo ) is either used for animal feed or is discarded. The aim of this research was to study the effect of bergamot Pastazzo flour in shortbread biscuits. Pastazzo flour partially replaced the 00 wheat flour in different percentages (2.5%, 5%, 10% and 15%). Simultaneously, a sample without the addition of Pastazzo flour (control) was analyzed, thus obtaining five biscuit samples. Cooking was done in a ventilated oven at 180 °C. The baking time was different for the control and the enriched samples depending on when the desired color was reached. The control took 12 min, while the enriched samples reached the desired color in 8 min. All samples were subjected to physicochemical and antioxidant characterization, as well as total polyphenols and flavonoids. The use of Pastazzo flour resulted in a slight increase in water activity and humidity values. pH values decreased for all the enriched samples compared to the control, but this was more relevant for the samples enriched with 10 and 15% of flour from by-products. Hardness varied from 1823 g (Control) to 2022 and 2818 g (respectively, for 2.5% and 15% bergamot Pastazzo flour in the recipe). Total phenol content varied from 0.14 mg GAE g -1 (Control) to 0.60 and 3.64 mg GAE g -1 (respectively, for 2.5% and 15% bergamot Pastazzo flour in the recipe). The obtained results demonstrated that the use of Pastazzo flour had a positive influence on the antioxidant content, with values which increased as more Pastazzo flour was added.

Background: Behavioral and psychological symptoms of dementia (BPSD) have a large impact on the quality of life of patients with Alzheimer's disease (AD). Few studies have compared BPSD between early-onset (EOAD) and late-onset (LOAD) patients, finding conflicting results., Objective: The aims of this study were to: 1) characterize the presence, overall prevalence, and time of occurrence of BPSD in EOAD versus LOAD; 2) estimate the prevalence over time and severity of each BPSD in EOAD versus LOAD in three stages: pre-T0 (before the onset of the disease), T0 (from onset to 5 years), and T1 (from 5 years onwards); 3) track the manifestation of BPSD sub-syndromes (i.e., hyperactivity, psychosis, affective, and apathy) in EOAD versus LOAD at T0 and T1., Methods: The sample includes 1,538 LOAD and 387 EOAD diagnosed from 1996 to 2018. Comprehensive assessment batteries, including the Neuropsychiatric Inventory (NPI), were administered at the first medical assessment and at different follow-up period., Results: The overall prevalence for the most of BPSD was significantly higher in EOAD compared to LOAD whereas most BPSD appeared significantly later in EOAD patients. Between the two groups, from pre-T0 to T1 we recorded a different pattern of BPSD prevalence over time as well as for BPSD sub-syndromes at T0 and T1. Results on severity of BPSD did not show significant differences., Conclusion: EOAD and LOAD represent two different forms of a single entity not only from a neuropathological, cognitive, and functional level but also from a psychiatric point of view.

Mutation A713T in the amyloid precursor protein (APP) has been linked to cases of Alzheimer's disease (AD), cerebral amyloid angiopathy (CAA) and cerebrovascular disease. Despite its rarity, it has been observed in several families from the same geographical area, in the Calabria region in Southern Italy. Genotyping of 720,000 genome-wide SNPs with the HumanOmniExpress BeadChip was performed for six patients that were representative of apparently unrelated Calabrian families, as well as a Belgian subject of Italian descent (all with the same A713T mutation and disease). Their genomic structure and genetic relationships were analyzed. Demographic reconstruction and coalescent theory were applied to estimate the time of the most recent common ancestor (tMRCA) among patients. Results show that all A713T carriers fell into the genetic variability of Southern Italy and were not more closely related to each other than to any other healthy Calabrian individual. However, five out of seven patients shared a 1.7 Mbp-long DNA segment centered on the A713T mutation, making it possible to estimate a tMRCA for its common origin in the Calabrian region dating back over 1000 years. The analysis of affected individuals with methodologies based on human population genomics thus provides informative insights in support of clinical observations and biomedical research.

Inclusion body myopathy (IBM) with Paget's disease of bone (PDB) and/or frontotemporal dementia (FTD) (IBMPFD) was recently identified as rare autosomal dominant disorder due to mutations in VCP gene. However, VCP mutations have also been documented in patients with amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth type 2 (CMT2) disease, and hereditary spastic paraplegia (HSP), underlining the heterogeneity of the phenotypes due to VCP mutations. In this study, we reported a novel missense heterozygous variant c.1184A > C ( p .D395A) in exon 10 of VCP gene identified in three patients (two sisters and one brother) belonging to an Italian family. The patients underwent a detailed clinical evaluation including medical history, neurological examination, and neuropsychological assessment. Brain's morphologic and functional analysis was also performed. The whole picture was consistent with the criteria of behavioral variant frontotemporal dementia (bvFTD) without IBM and PBD. Our report confirms the high degree of heterogeneity of VCP disease. A VCP analysis should be considered for the genetic screening of familial bvFTD with an early onset also in absence of IBM or PDB signs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bruno, Conidi, Puccio, Frangipane, Laganà, Bernardi, Smirne, Mirabelli, Colao, Curcio, Di Lorenzo, Maletta and Bruni.)

Background: Family caregivers of patients with dementia are at high risk of stress and burden, and quarantine due to the coronavirus disease 2019 (COVID-19) pandemic may have increased the risk of psychological disturbances in this population. The current study was carried out during the national lockdown declared in March 2020 by the Italian government as a containment measure of the first wave of the coronavirus pandemic and is the first nationwide survey on the impact of COVID-19 lockdown on the mental health of dementia informal caregivers. Methods: Eighty-seven dementia centers evenly distributed on the Italian territory enrolled 4,710 caregiver-patient pairs. Caregivers underwent a telephone interview assessing classical symptoms of caregiver stress and concern for the consequences of COVID-19 infection on patient's health. We calculated prevalence of symptoms and regressed them on various potential stress risk factors: caregivers' sociodemographic characteristics and lifestyle, patients' clinical features, and lockdown-related elements, like discontinuity in medical care. Results: Approximately 90% of caregivers reported at least one symptom of stress, and nearly 30% reported four or more symptoms. The most prevalent symptoms were concern for consequences of COVID-19 on patient's health (75%) and anxiety (46%). The main risk factors for stress were identified as a conflicting relationship with the patient and discontinuity in assistance, but caregiver's female sex, younger age, lower education, and cohabitation with the patient also had an impact. Availability of help from institutions or private individuals showed a protective effect against sense of abandonment but a detrimental effect on concern about the risk for the patient to contract COVID-19. The only protective factor was mild dementia severity, which was associated with a lower risk of feeling isolated and abandoned; type of dementia, on the other hand, did not affect stress risk. Conclusion: Our results demonstrate the large prevalence of stress in family caregivers of patients with dementia during the COVID-19 pandemic and have identified both caregivers and situations at a higher risk of stress, which should be taken into account in the planning of interventions in support of quarantined families and patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zucca, Isella, Lorenzo, Marra, Cagnin, Cupidi, Bonanni, Laganà, Rubino, Vanacore, Agosta, Caffarra, Sambati, Quaranta, Guglielmi, Appollonio, Logroscino, Filippi, Tedeschi, Ferrarese, Rainero, Bruni and the SINdem COVID-19 Study Group.)

Introduction: Previous studies showed that quarantine for pandemic diseases is associated with several psychological and medical effects. The consequences of quarantine for COVID-19 pandemic in patients with dementia are unknown. We investigated the clinical changes in patients with Alzheimer's disease and other dementias, and evaluated caregivers' distress during COVID-19 quarantine., Methods: The study involved 87 Italian Dementia Centers. Patients with Alzheimer's Disease (AD), Dementia with Lewy Bodies (DLB), Frontotemporal Dementia (FTD), and Vascular Dementia (VD) were eligible for the study. Family caregivers of patients with dementia were interviewed by phone in April 2020, 45 days after quarantine declaration. Main outcomes were patients' changes in cognitive, behavioral, and motor symptoms. Secondary outcomes were effects on caregivers' psychological features., Results: 4913 patients (2934 females, 1979 males) fulfilled the inclusion criteria. Caregivers reported a worsening in cognitive functions in 55.1% of patients, mainly in subjects with DLB and AD. Aggravation of behavioral symptoms was observed in 51.9% of patients. In logistic regression analysis, previous physical independence was associated with both cognitive and behavioral worsening (odds ratio 1.85 [95% CI 1.42-2.39], 1.84 [95% CI 1.43-2.38], respectively). On the contrary, pandemic awareness was a protective factor for the worsening of cognitive and behavioral symptoms (odds ratio 0.74 [95% CI 0.65-0.85]; and 0.72 [95% CI 0.63-0.82], respectively). Approximately 25.9% of patients showed the onset of new behavioral symptoms. A worsening in motor function was reported by 36.7% of patients. Finally, caregivers reported a high increase in anxiety, depression, and distress., Conclusion: Our study shows that quarantine for COVID-19 is associated with an acute worsening of clinical symptoms in patients with dementia as well as increase of caregivers' burden. Our findings emphasize the importance to implement new strategies to mitigate the effects of quarantine in patients with dementia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rainero, Bruni, Marra, Cagnin, Bonanni, Cupidi, Laganà, Rubino, Vacca, Di Lorenzo, Provero, Isella, Vanacore, Agosta, Appollonio, Caffarra, Bussè, Sambati, Quaranta, Guglielmi, Logroscino, Filippi, Tedeschi, Ferrarese and the SINdem COVID-19 Study Group.)

Background: In March 2020, the World Health Organization declared a global pandemic due to the novel coronavirus SARS-CoV-2 and several governments planned a national quarantine in order to control the virus spread. Acute psychological effects of quarantine in frail elderly subjects with special needs, such as patients with dementia, have been poorly investigated. The aim of this study was to assess modifications of neuropsychiatric symptoms during quarantine in patients with dementia and their caregivers., Methods: This is a sub-study of a multicenter nation-wide survey. A structured telephone interview was delivered to family caregivers of patients with diagnosis of Alzheimer disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and vascular dementia (VD), followed regularly at 87 Italian memory clinics. Variations in behavioral and psychological symptoms (BPSD) were collected after 1 month since quarantine declaration and associations with disease type, severity, gender, and caregiver's stress burden were analyzed., Results: A total of 4,913 caregivers participated in the survey. Increased BPSD was reported in 59.6% of patients as worsening of preexisting symptoms (51.9%) or as new onset (26%), and requested drug modifications in 27.6% of these cases. Irritability, apathy, agitation, and anxiety were the most frequently reported worsening symptoms and sleep disorder and irritability the most frequent new symptoms. Profile of BPSD varied according to dementia type, disease severity, and patients' gender. Anxiety and depression were associated with a diagnosis of AD (OR 1.35, CI: 1.12-1.62), mild to moderate disease severity and female gender. DLB was significantly associated with a higher risk of worsening hallucinations (OR 5.29, CI 3.66-7.64) and sleep disorder (OR 1.69, CI 1.25-2.29), FTD with wandering (OR 1.62, CI 1.12-2.35), and change of appetite (OR 1.52, CI 1.03-2.25). Stress-related symptoms were experienced by two-thirds of caregivers and were associated with increased patients' neuropsychiatric burden (p<0.0001)., Conclusion: Quarantine induces a rapid increase of BPSD in approximately 60% of patients and stress-related symptoms in two-thirds of caregivers. Health services need to plan a post-pandemic strategy in order to address these emerging needs., (Copyright © 2020 Cagnin, Di Lorenzo, Marra, Bonanni, Cupidi, Laganà, Rubino, Vacca, Provero, Isella, Vanacore, Agosta, Appollonio, Caffarra, Pettenuzzo, Sambati, Quaranta, Guglielmi, Logroscino, Filippi, Tedeschi, Ferrarese, Rainero, Bruni and SINdem COVID-19 Study Group.)

Background: The Early Childhood Attention Battery (ECAB) has been used to assess three different components of attention in preschool children, namely, selective, sustained and attentional control., Aim: The aim of the study was: I) to adapt the ECAB to the Italian language; II) to collect Italian reference data using the translated version and III) to expand the available reference data using 6-month age intervals., Study Design: The adaptation of the ECAB to Italian language and the collection of Italian reference data was performed in four phases: translation and identification of the manual and subtests that needed adaptation; interobserver reliability and feasibility of the Italian version; application of the Italian ECAB; statistical analysis., Subjects: The ECAB was performed on a low risk population between 3 and 5 years, 11 months., Results: Statistical analysis was conducted subdividing the cohort in 6-month age groups. The final cohort included 300 low-risk typically developing children. The assessment was well accepted and enjoyed by most of the children except for some in the youngest group who refused to complete all of the tests. Our data showed a progressive improvement in attention across age in seven of the eight subtests of the ECAB., Conclusion: The ECAB is a feasible battery in Italian as in the English version, for the assessment of early attention in preschool children, allowing the assessment of the different components of attention and a specific maturation follow up with increasing age., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Dentatorubral-pallidoluysian atrophy is a hereditary neurodegenerative disease prevalently reported in Japan but rare in Caucasians. The objective of this study was to reconstruct the pedigree of Italian dentatorubral-pallidoluysian atrophy familial cases describing their clinical features., Methods: We investigated 6 apparently unrelated dentatorubral-pallidoluysian atrophy families comprising a total of 51 affected individuals: 13 patients were clinically examined, and for 38 patients clinical data were collected from clinical sources. The dentatorubral-pallidoluysian atrophy diagnosis was genetically confirmed in 18 patients. Genealogical data from historical archives were analyzed., Results: All 6 families were unified in a large pedigree deriving from a founder couple originating from Monte San Giuliano (Italy) in the late 1500s, with 51 affected subjects over the last 4 generations. Wide phenotypical variability in age at onset and clinical features was confirmed. Epilepsy was more frequent in juvenile cases than in late adults, with cognitive/psychiatric and motor disorders observed regardless of age at onset., Conclusions: We have described the largest Caucasian dentatorubral-pallidoluysian atrophy pedigree from a single founder couple. The introduction of the dentatorubral-pallidoluysian atrophy gene in Italy could have arisen as a result of trade relationships between the Spanish or Portuguese and the Japanese in the 1500s. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)

Background: Delirium is a multifactorial geriatric syndrome and often occurs in patients with cognitive impairment. It also remains under-recognized, specifically in elderly outpatients, because signs of delirium might overlap with symptoms of dementia., Objective: The aim of the present study is to retrospectively apply the chart-based delirium instrument on a cohort of elderly outpatients with dementia, to assess prevalence and features of delirium in this population., Methods: We randomly selected 650 medical records of outpatients referred to the "Neurogenetic Regional Centre" (CRN) of Lamezia Terme. Each evaluation included demographics, medical history, drugs, type and severity of dementia, and cognitive and functional status. Delirium was identified by the application of the chart-based delirium instrument., Results: The prevalence of delirium was 13.3%. The study population was divided, according to the presence of delirium, into two subgroups. Compared to the no delirium group, the delirium group was significantly older and had greater cognitive impairment with lower MMSE scores both at baseline and at the end of the follow up. They also had a significant lower score on the ADL and IADL. In this group, a higher intake of antihypertensive and antipsychotic drugs, together with a lower intake of cholinesterase inhibitors and memantine, was observed., Conclusions: In this study, the chart-based delirium instrument was applied to an outpatient population affected by dementia and followed for a long time. Our data confirm the importance that age and frailty play on the genesis of delirium and suggest attention should be paid to the pharmacological treatment of these patients.

Background: Several genetic variants playing a key role in cholesterol levels, blood pressure, and vascular dysfunction influence the risk of Alzheimer's disease (AD) and vascular dementia (VaD). The many meta-analysis studies carried out on large numbers of samples in different populations have not provided clear results to date, because a trans-ethnic shift of risk genotypes in different populations is often observed., Objectives: To determine genotypes allele frequencies of the polymorphisms most frequently identified to be correlated with cardio-cerebrovascular disease and AD in a Southern Italy population and to investigate their possible association with dementia., Methods: The genotype and allele frequencies of 13 cardio-cerebrovascular risk polymorphisms were assessed and their possible association with dementia was investigated in a case-control study, including 221 consecutive unrelated subjects diagnosed with dementia (120 subjects affected by AD, 55 by frontotemporal dementia, and 33 by vascular dementia) and 218 matched controls of Calabrian origin., Results: Carriers of at least one APOEɛ4 allele resulted to be at higher risk of AD [OR(95% CI) = 2.721(1.477-5.011)] and VaD [OR(95% CI) = 6.205(2.356-16.342)] compared to non-carriers. Individuals with the IV genotype of the CETP polymorphism were more likely to have AD [OR(95% CI) = 2.427(1.364-4.319)] and VaD [OR(95% CI) = 3.649(1.455-9.152)] compared to subjects with the II-VV genotypes., Conclusion: CETP I405V polymorphism is likely a risk factor for AD and VaD in our cohort, independent of APOEɛ4 status. Unmodifiable genetic risk factors should be taken into account to promote a healthy lifestyle to prevent dementia.

We identified the novel PSEN1 pathogenic mutation M84V in 3 patients belonging to a large kindred affected by autosomal dominant Alzheimer's disease (AD). The clinical phenotype was characterized by early onset dementia in 14 affected subjects over 3 generations. Detailed clinical, imaging and genetic assessment was performed. We highlighted the presence of unusual symptoms such as frontal executive syndrome, psychosis and spastic paraparesis in these patients. Spastic paraparesis has been reported in other PSEN1 mutations in adjacent codons, suggesting that the position of the genetic defect may affect the clinical expression, although this phenotype can occur in mutations throughout the whole PSEN1 gene. Brain magnetic resonance imaging showed diffuse cortical atrophy, but also atrophy of cerebellar lobules, mainly involving Crus I, in 2 patients without cerebellar motor deficits. These neuroimaging results were consistent with recent findings about the association between sporadic AD and distinct and circumscribed cerebellar atrophy. The present work acknowledged the novel PSEN1 pathogenic mutation M84V and might contribute to the ongoing debate about the involvement of cerebellum in AD., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The rebuilding of the N family, a large Italian kindred affected by early-onset autosomal dominant Alzheimer's disease (AD), provided an important contribution to the discovery of Presenilin 1 (PSEN1), the main gene responsible for familial AD. This pedigree was identified with the help of medical records from the archives of the Psychiatric Hospital of Girifalco, Italy. The clinical record of Angela R., an ancestor of the N family, dating back to 1904, showed a clinical picture of Angela R., consistent with a diagnosis of non-amnestic probable AD, matching the "dysexecutive" phenotype described in her descendants. The a posteriori diagnosis of AD is supported by the evidence of the causative genetic mutation PSEN1-Met146Leu as well as neuropathological AD features in her genealogically proven descendants. The clinical case of Angela R. was recorded at the same time of Alzheimer's description of Auguste D. Its discovery crucially contributed to the genealogical reconstruction of the N family, linking came from different branches, which until then were unrelated, to the same kindred. The archives of the Girifalco Hospital represented a valuable source of medical and historical information and were essential to the research on Italian-American AD families that finally led to the identification of new genes.